This project will use an animal model system for Crohn's disease to characterize the basic factors involved in chronic granulomatous enteritis. The purpose of this project is to determine the levels of production of Interleukin 1 (IL-1) by monocytes and macrophages from cattle with histologically and culturally confirmed naturally occurring mycobacterial enteritis due to M. paratuberculosis. The influence of plasma inhibitory factors on the expression of IL-1 activity will also be measured. Cells from peripheral blood and from in situ macrophage collectors will be tested in vitro for IL-1 using the mouse thymocyte assay. It is hypothesized that the marked diffuse granulomatous inflammatory responses occur in the absence of proper mediation by lymphoid cells to cure or control the infectious process due to a lack of IL-1 production or interference with IL-1 release. Clarification of the ability of macrophages to activate lymphoid cells or fibroblasts will aid in the elucidation of the defective immunological mechanism which allows unchecked proliferation of the mycobacteria with ineffective and nonprotective granuloma formation. In addition, this project will develop a foundation of basic knowledge of ruminant paratuberculosis necessary for extending the usefulness of this disease in cattle as an animal model for Crohn's disease, leprosy and the opportunistic mycobacterial enteritis in the acquired immunodeficiency syndrome (AIDS). Clarification of the pathogenesis of the lesions in JD will also enable the interpretation of effects due to pharmacological and immunopharmacological therapies.